The technique of ion microscopy will be applied to a number of biomedical problems for the study of intracellular localization of elemental distribution and ion transport. Much of the proposed research depends on the unique isotopic imaging capability of the ion microscope, and represents the culmination of our continued efforts to demonstrate the problem solving capabilities of ion microscopy in biology and medicine. Stable isotopes of calcium and magnesium will be used in conjunction with cryosample preparation methodologies for understanding a number of fundamental and applied collaborative biomedical problems. Enriched stable (44)Ca and (26)Mg isotopes will be used to study the basic phenomenon of cellular calcium and magnesium exchange at the subcellular level in tissue culture cells. In collaboration with researchers at Cornell, the ion microscope will be used to understand intestinal, calcium absorption using (44)Ca as a tracer for calcium transport. (44)Ca will also be used to investigate the complex role of calcium in the secretory response of mast cells during the allergic reaction. In another collaborative biomedical study, the multielement imaging capability of the ion microscope will be used to screen neuronal populations for the existence of functional neurotransmitter receptors. A successful completion of this program would not only provide important new information regarding the proposed biomedical studies, but also establish ion microscopy as an essential technique in many subcellular ion transport related studies previously unattainable.